Intestinal Cell News 4.41 October 26, 2018 | |
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TOP STORYDeregulation of CRAD-Controlled Cytoskeleton Initiates Mucinous Colorectal Cancer via β-Catenin Researchers identified cancer-related regulator of actin dynamics (CRAD) as frequently mutated or transcriptionally downregulated in colorectal cancer. They found that CRAD stabilizes the cadherin-catenin-actin complex via capping protein inhibition. [Nat Cell Biol] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Deacetylation of Serine Hydroxymethyl-Transferase 2 by SIRT3 Promotes Colorectal Carcinogenesis Investigators observed that serine hydroxymethyltransferase 2 (SHMT2) is acetylated at K95 in colorectal cancer cells. SIRT3, the major deacetylase in mitochondria, was responsible for SHMT2 deacetylation. SHMT2-K95-Ac disrupted its functional tetramer structure and inhibited its enzymatic activity. [Nat Commun] Full Article PPAPDC1A fusions and in-frame fusions containing a RhoGAP domain clearly defined the aggressive subset of diffuse gastric cancers, and their prognostic impact was greater than, and independent of, chromosomal instability and CDH1 mutations. [Nat Commun] Full Article To identify the initiator of inflammatory host-microbiome cross-talk, researchers leveraged a pathomimetic “gut inflammation-on-a-chip” undergoing physiological flow and motions that recapitulates the pathophysiology of dextran sodium sulfate-induced inflammation in murine models. [Proc Natl Acad Sci USA] Abstract | Press Release Regnase-1 Controls Colon Epithelial Regeneration via Regulation of mTOR and Purine Metabolism During dextran sulfate sodium-induced intestinal epithelial injury and acute colitis, Regnase-1∆IEC mice, which lack Regnase-1 specifically in the intestinal epithelium, were resistant to body weight loss, maintained an intact intestinal barrier, and showed increased cell proliferation and decreased epithelial apoptosis. [Proc Natl Acad Sci USA] Full Article Investigators found that Stat6−/− mice developed more tumors in the colitis-associated carcinogenesis model. This was accompanied by a more pronounced inflammatory response during colitis and an elevated Stat3-dependent proliferation of intestinal epithelial cells. [Oncogene] Full Article The bromodomain inhibitor JQ1 suppressed interferon-stimulated gene (ISG) expression and in combination with MEK inhibitors (MEKi) displayed synergistic effects and induced apoptosis in MEKi-resistant colorectal cancer cell lines. ISG expression was confirmed in patient-derived organoid models, which displayed resistance to trametinib and were resensitized by JQ1 co-treatment. [Oncogene] Full Article PARP Inhibition Sensitizes Colorectal Cancer‐Initiating Cells to Chemotherapy Small molecule poly‐ADP‐ribose polymerase inhibitors (PARPi) sensitized colorectal cancer‐initiating cells (CICs) to chemotherapy and reduced chemotherapy‐treated CIC viability, self‐renewal, and DNA damage repair. While PARPi monotherapy failed to kill CICs, combined PARPi therapy with chemotherapy attenuated tumor growth in vivo. [Stem Cells] Abstract Mice with intestinal epithelial cell (IEC)-specific depletion of MOB kinase activator 1A/1B (MOB1A/B) showed hyperproliferation in intestinal epithelial cells, defects in secretory lineage differentiation and loss of intestinal stem cells and eventually died at 10-12 days after tamoxifen treatment. [Cell Death Dis] Full Article Scientists used AOM/DSS model, the clinicopathological features are similar to those found in humans, to investigate the effects of metformin as well as combination with 5-FU in the prevention of colitis and CAC. [Cancer Biol Ther] Abstract Actin-like 6A (ACTL6A) overexpression promoted migration and invasion of colon cancer cells, whereas ACTL6A knockdown exhibited the opposite effect in vitro. [BMC Cancer] Full Article The authors characterized induced pluripotent stem cell-derived human intestinal epithelial organoids by comparing these cultures with primary purified intestinal epithelial cells. [Cell Mol Gastroenterol Hepatol] Full Article Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News. | |
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REVIEWSCancer Pharmacoprevention: Targeting Polyamine Metabolism to Manage Risk Factors for Colon Cancer Researchers discuss the role of polyamines in colon cancer and highlight the mechanisms of select pharmacoprevention agents to delay or prevent carcinogenesis in humans. [J Biol Chem] Abstract | Full Article Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
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SCIENCE NEWSOncolytics Biotech® Inc. announced positive clinical trial results for pelareorep in the treatment of patients with KRAS mutant metastatic colorectal cancer. Patients receiving treatment with the recommended Phase II dose of pelareorep in combination with FOLFIRI/B had progression free survival of 65.6 weeks and an overall survival of 107.5 weeks, which exceeded expectations when compared to historical data. [Press release from Oncolytics Biotech® discussing research presented at the Annual European Society for Medical Oncology (ESMO) 2018 Congress, Munich] Press Release | |
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INDUSTRY NEWSTakeda Pharmaceutical Company Limited announced results from the Phase III VISIBLE 1 clinical trial evaluating the efficacy and safety of an investigational subcutaneous formulation of the gut-selective biologic vedolizumab for maintenance therapy in adult patients with moderately to severely active ulcerative colitis who achieved clinical response at week six following two doses of open-label vedolizumab intravenous induction therapy. [Takeda Pharmaceutical Company Limited] Press Release Bristol-Myers Squibb Company announced new data from a cohort of the CheckMate -142 study in which Opdivo plus low-dose Yervoy demonstrated durable clinical benefit as a first-line treatment in patients with microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) metastatic colorectal cancer. [Bristol-Myers Squibb Company] Press Release Spectrum Pharmaceuticals Receives FDA Approval of KHAPZORY™ (Levoleucovorin) for injection Spectrum Pharmaceuticals, Inc. announced that the FDA has approved KHAPZORY for injection for rescue after high-dose methotrexate therapy in patients with osteosarcoma, diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination and the treatment of patients with metastatic colorectal cancer in combination with fluorouracil. [Spectrum Pharmaceuticals, Inc.] Press Release | |
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POLICY NEWSA flood of candidates with scientific, technical, and health backgrounds decided to run this year for the U.S. House of Representatives. All but one is a Democrat, and many were reacting to the 2016 election of President Donald Trump and the policies of the Republican majority in Congress. [ScienceInsider] Editorial Font of Despair: In the Fierce Competition for Science Funding, Even a Typeface Glitch Can Be Fatal To those experienced in requesting cash from both the Department of Veterans Affairs and the National Institutes of Health, rejection on the basis of margin or serif, if not the most pressing problem in biomedical research, is unsurprising and frustrating. [STAT News] Editorial What a Massive Database of Retracted Papers Reveals about Science Publishing’s ‘Death Penalty’ Nearly a decade ago, headlines highlighted a disturbing trend in science: The number of articles retracted by journals had increased 10-fold during the previous 10 years. Fraud accounted for some 60% of those retractions; one offender, anesthesiologist Joachim Boldt, had racked up almost 90 retractions after investigators concluded he had fabricated data and committed other ethical violations. [ScienceInsider] Editorial
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EVENTSNEW Gordon Research Conference: Stem Cells and Cancer Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Associate Professor – Oncology (University of California, Davis) NEW Postdoctoral Fellow – Patient Derived Organoids (Rutgers Cancer Institute of New Jersey) PhD Studentship – Gastrointestinal Adenocarcinomas (University of Cambridge) Research Associate – Gut Signaling and Metabolism (Imperial College London) Postdoctoral Position – Dendritic Cell Biology & Antigen Presentation (Weill Cornell Medicine) Group Leader – Organoid Modeling of Disease (European Molecular Biology Laboratory) Postdoctoral Position – Colon Cancer Research (Vanderbilt University Medical Center) Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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